Thrombopoietin and its splicing variants: structure and functions in thrombopoiesis and beyond.

Since its cloning in 1994, several studies have reported that thrombopoietin (THPO) presents several alternative splicing products that differ from the full-length protein in its 5' UTR, N- or C-terminal regions. Most of these splice variants are evolutionarily conserved and have been detected in different tissues as well as in cell lines. Although the possible functions of the THPO isoforms are still elusive, different clues link them to the peculiar mechanism that regulates THPO production. Moreover, novel fields to explore possible roles of the THPO variants are opened by observations that this hormone can influence the formation of hematopoietic progenitors and its expression occurs in some tumors as well as in tissues not directly related to the thrombopoiesis. In this review, we summarize the structure and functions of THPO through the published evidence on its splicing isoforms and discuss about their involvement with physiopathologic phenomena.